During the past year we have carried out a survey of several tumor-inducing agents for their ability to produce macromolecular complexes in vitro. Using several independent techniques (including gel electrophoresis; velocity and equilibrium centrifugation at various pH's, with and without ionic detergents; and chromatography on methyl-esterified albumin) we have found that all ultimate carcinogenic agents tested thus far fall into two broad categories: (A) chemicals which are capable of inducing complexes between nucleic acids and nucleic acids and proteins; and (B) those which induce the protein-nucleic acid adducts only. Most mono- and polyfunctional alkylating agents and chromium salts belong to class A. Aromatic amines, salts of beryllium and ultraviolet light, are examples of class B agents. Non-ultimate carcinogenic chemicals produce no macromolecular complexes under our experimental conditions, but form such complexes following their activation by liver extracts (postmitochondrial supernatants). These observations suggest that formation of strong bonds between macromolecules may be involved in the process of tumor induction, possibly by interfering with normal disjunction of sister chromosomes during mitosis. We plan to study the effects of carcinogenic chemicals on DNA and RNA in living cells and in particular to test for the formation of similar complexes in vivo and to study means of elimination of such structures from the injured tissue. In parallel, our present studies on the effects of carcinogens on biologically active (transforming) DNA will be continued. We also plan further practical applications of our observations on the increased cellular attachment of nucleic acids exposed to carcinogens and mutagens. Our survey of several agents suggests that this technique may be used as a very simple and inexpensive means of detection of carcinogenic agents in our environment. BIBLIOGRAPHIC REFERENCES: H. Kubinski, P.E. Zeldin and N.R. Morin: Survey of Tumor-producing Agents for their Ability to Induce Macromolecular Complexes. AACR Meeting, Denver, Colo., 1977. H. Kubinski, Z.O. Kubinski and N.R. Morin: Physicochemical Changes in DNA Exposed to Alkylating Carcinogens and Mutagens. FASEB Meeting, Chicago, Ill., 1977.